Leukocyte-endothelial adhesion in the pathogenesis of inflammation
- Amos Etzioni, MD
Amos Etzioni, MD
- Professor of Pediatrics and Immunology
- The Rappaport Faculty of Medicine, Technion, Haifa
Inflammation is a crucial process in the normal defense mechanisms against various pathogens, and leukocytes are the principal cellular mediators of inflammation. Inflammation is characterized histologically by the accumulation of leukocytes in the affected tissue due to migration of circulating leukocytes out of the vasculature, a process which is actively mediated and precisely controlled by leukocytes, the cytokines they produce, and the vascular endothelium . However, excessive or uncontrolled inflammatory responses can lead to the pathologic inflammation seen in many rheumatologic and inflammatory disorders.
Leukocyte trafficking from the blood stream into tissue is important for surveillance of foreign antigens and for rapid leukocyte accumulation at a site of inflammatory response or tissue injury. Although the importance of leukocyte movement towards sites of inflammation was well recognized more than a century ago, the precise molecular mechanisms for leukocyte interactions with the endothelium and the emigration of these cells through the endothelium were elucidated only decades later .
The process of leukocyte-endothelial adhesion during inflammation and the various adhesion molecules involved will be discussed in this topic review. Defects and deficiencies in adhesion molecules are presented separately. (See "Leukocyte-adhesion deficiency".)
Leukocyte-endothelial adhesion involves dynamic interactions between leukocytes and endothelial cells, involving multiple steps. These steps must be precisely orchestrated to ensure a rapid response with only minimal damage to healthy tissue . Interactions between leukocytes and the endothelium are mediated by several families of adhesion molecules, each of which participates in a different phase of the process. The surface expression and activation of these molecules during an inflammatory response is tightly controlled under normal conditions .
Three families of adhesion molecules are of particular importance to the process of leukocyte-endothelial adhesion (table 1):
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- ADHESION MOLECULES
- - Selectin ligands
- - Beta 1 integrins
- - Beta 2 integrins
- Immunoglobulin superfamily molecules
- THE ADHESION CASCADE
- Leukocyte activation and arrest
- - Defects in integrin activation
- Crawling and transmigration
- CLINICAL APPLICATIONS